Neurovascular lesions, such as aneurysms and arteriovenous malformations (AVMs), are insidious and unpredictable. They often go unnoticed until the occurrence of a catastrophic hemorrhage or stroke. Approximately 350,000 patients experience hemorrhage annually, resulting in permanent loss of motor function, seizures, and death. Current neurosurgical therapies are risky and often ineffective at removing the life-threatening condition. The purpose of this venture is to provide an innovative biomaterial for treating neurovascular lesions from inside the vessel (endovascular embolization) in order to significantly increase therapeutic effectiveness while minimizing the surgical risks. The goal of this proposal is to complete the development and testing of calcium alginate (ALGEL (R)) in preparation for aneurysm treatment clinical trials. First, current in vitro aneurysm models will be utilized to test ALGEL occlusion properties in aneurysms of various sizes. The aneurysm model will be occluded with three novel techniques: ALGEL injection combined with aneurysm coils, coating of coils with ALGEL to increase the volume of occlusion, and modification of coils to release activator to control the gelation of ALGEL within the aneurysm sac. The three techniques will be assessed for controllability, % filling of the aneurysm sac, and mechanical stability. Second, ALGEL's mechanical stability and biocompatibility will be assessed using FDA-approved pre-clinical guidelines. Shear resistance and fatigue resistance will be determined using Instron compression testing and rheometer dynamic shear testing to determine strength and degradation over time. ALGEL will also undergo a standard battery of ISO-10993 and ASTM protocols that include short-term studies such as cytotoxicity, system toxicity, irritation, hemolysis, and 1-month implantation. Long-term studies will include sub-chronic (3 months) toxicity and chronic (6 months) toxicity studies. The outcomes of the proposed project will be a solid foundation for the eventual development of safer and more effective treatments for life threatening aneurysms. We are guardedly optimistic for the potential of ALGEL because of the strength of earlier work and the robustness of the research and development plan. We feel that it is highly likely that ALGEL will turn out to be a clinically useful material.